Pediatric Hematology and Oncology
ISSN: 0888-0018 (Print) 1521-0669 (Online) Journal homepage: http://www.tandfonline.com/loi/ipho20
Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years Inci Yildiz, Nihal Ozdemir, Tiraje Celkan, Selen Soylu, Serap Karaman, Aylin Canbolat, Omer Dogru, Ethem Erginoz & Hilmi Apak To cite this article: Inci Yildiz, Nihal Ozdemir, Tiraje Celkan, Selen Soylu, Serap Karaman, Aylin Canbolat, Omer Dogru, Ethem Erginoz & Hilmi Apak (2015): Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years, Pediatric Hematology and Oncology, DOI: 10.3109/08880018.2015.1040931 To link to this article: http://dx.doi.org/10.3109/08880018.2015.1040931
Published online: 08 Jul 2015.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipho20 Download by: [ECU Libraries]
Date: 11 September 2015, At: 20:46
Pediatric Hematology and Oncology, Early Online:1–9, 2015 C Informa Healthcare USA, Inc. Copyright ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2015.1040931
ORIGINAL ARTICLE
Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years
Downloaded by [ECU Libraries] at 20:46 11 September 2015
Inci Yildiz,1 Nihal Ozdemir,1 Tiraje Celkan,1 Selen Soylu,1 Serap Karaman,1 Aylin Canbolat,1 Omer Dogru,1 Ethem Erginoz,2 and Hilmi Apak1 1
Department of Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey; 2 Department of Public Health, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years’ experience for first-line therapy of acute ITP. Five hundred fortyone children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 109 /L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids. Keywords bleeding diathesis, childhood, immune thrombocytopenia, thrombocytopenia
INTRODUCTION Immune thrombocytopenia (ITP), or Werlhoff disease as it was historically called, is a common acquired hemorrhagic disorder of adults and children characterized by transient or persistent decrease of the platelet count in the absence of other causes that may be associated with thrombocytopenia [1]. The majority of ITP has an acute presentation, and 80%–90% of the cases will recover spontaneously or with therapy [2]. Ten percent to 20% of the cases have a chronic course. Recently, new categories of “newly diagnosed” or “persistent” ITP have been recommended instead of previous Received 4 June 2014; accepted 10 April 2015. Address correspondence to Nihal Ozdemir, I.U. Cerrahpasa Tip Fakultesi Hastanesi, C ¸ ocuk Hematoloji BD, 34098 Fatih/Cerrahpasa, Istanbul, Turkey. E-mail: [email protected]
Downloaded by [ECU Libraries] at 20:46 11 September 2015
I. Yildiz et al.
terms of “acute” and “chronic” ITP [1]. The etiology is unknown, but the newly diagnosed ITP may follow an antigenic challenge such as infection or vaccination within a few weeks. The immune mechanisms that play role in the initiation of the disease are the targets of therapy when indicated. There are several treatment strategies used for the newly diagnosed patients as firstline therapy, including observation alone, corticosteroids, intravenous immunoglobulin (IVIG), and anti-RhD immunoglobulin (anti-D IgG). High-dose pulse methylprednisone (HDMP) therapy was first used by Ozsoylu from Turkey [3–5] and other authors [6, 7] and was quite successful in raising the platelet counts. Imbach and Blanchette [8, 9] and their colleagues proposed high-dose IVIG treatment (0.8–1 g/kg) and showed a success rate of 80%. Other modalities of treatment include anti-D IgG therapy [10–13] and cytostatics such as vinca alkaloids and chlorambucil [14]. Splenectomy is usually reserved for children with persistent or refractory ITP when first-line treatment options fail [15]. New treatment modalities such as rituximab, eltrombopag, or romiplostim are currently used mostly in adult patients and more rarely in pediatric patients [16–18]. Although there are several guidelines published for the treatment of acute ITP, there is still considerable controversy on which pediatric patients should be treated and what is the most appropriate therapeutic agent. Observation is recommended unless the child has active bleeding and/or wet purpura; however, some physicians still choose to treat a platelet count for the rare risk of life-threatening bleeding or parent anxiety. Cerrahpasa Medical Faculty is a university hospital and tertiary center to where about 15–20 new cases of ITP are referred every year. The aim of this study is to present our own center’s experience of 32 years to evaluate the treatment options for this common disease. MATERIALS AND METHODS This retrospective study aimed to analyze children (3 months to 18 years) who were diagnosed and treated for ITP at Cerrahpasa Medical Faculty, Pediatric Hematology Unit, between 1978 and 2010. These included patients seen and treated at outpatient setting as well as children hospitalized for ITP. A total of 541 medical records were available for review. Demographic data, bleeding manifestations, any history of antecedent infection or vaccination, initial and follow-up platelet counts, treatment on the first visit, platelet response to therapy, complications related to ITP, and final outcome from the time of presentation were recorded. Because the patients included in this study were classified as acute/chronic before the newer terms were proposed and were managed accordingly, older classification was used for the purpose of this retrospective study. Chronic ITP was defined as thrombocytopenia persisting for longer than 6 months following initial diagnosis. Patients were also classified as acute ITP if their platelet counts normalized due to therapy (normal platelet count in the last 4 weeks without treatment) when they don’t have a follow-up platelet count at 6 months. Bone marrow aspiration, Coombs test, antiplatelet antibodies, antinuclear antibodies, viral serology, and immunoglobulins were investigated in selected cases. Bone marrow aspirates were performed in children with atypical features to exclude other hematological diseases or before initiation of corticosteroid treatment. Therapy at initial diagnosis was administered to patients with platelet counts
ISSN: 0888-0018 (Print) 1521-0669 (Online) Journal homepage: http://www.tandfonline.com/loi/ipho20
Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years Inci Yildiz, Nihal Ozdemir, Tiraje Celkan, Selen Soylu, Serap Karaman, Aylin Canbolat, Omer Dogru, Ethem Erginoz & Hilmi Apak To cite this article: Inci Yildiz, Nihal Ozdemir, Tiraje Celkan, Selen Soylu, Serap Karaman, Aylin Canbolat, Omer Dogru, Ethem Erginoz & Hilmi Apak (2015): Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years, Pediatric Hematology and Oncology, DOI: 10.3109/08880018.2015.1040931 To link to this article: http://dx.doi.org/10.3109/08880018.2015.1040931
Published online: 08 Jul 2015.
Submit your article to this journal
Article views: 21
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipho20 Download by: [ECU Libraries]
Date: 11 September 2015, At: 20:46
Pediatric Hematology and Oncology, Early Online:1–9, 2015 C Informa Healthcare USA, Inc. Copyright ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2015.1040931
ORIGINAL ARTICLE
Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years
Downloaded by [ECU Libraries] at 20:46 11 September 2015
Inci Yildiz,1 Nihal Ozdemir,1 Tiraje Celkan,1 Selen Soylu,1 Serap Karaman,1 Aylin Canbolat,1 Omer Dogru,1 Ethem Erginoz,2 and Hilmi Apak1 1
Department of Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey; 2 Department of Public Health, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years’ experience for first-line therapy of acute ITP. Five hundred fortyone children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 109 /L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids. Keywords bleeding diathesis, childhood, immune thrombocytopenia, thrombocytopenia
INTRODUCTION Immune thrombocytopenia (ITP), or Werlhoff disease as it was historically called, is a common acquired hemorrhagic disorder of adults and children characterized by transient or persistent decrease of the platelet count in the absence of other causes that may be associated with thrombocytopenia [1]. The majority of ITP has an acute presentation, and 80%–90% of the cases will recover spontaneously or with therapy [2]. Ten percent to 20% of the cases have a chronic course. Recently, new categories of “newly diagnosed” or “persistent” ITP have been recommended instead of previous Received 4 June 2014; accepted 10 April 2015. Address correspondence to Nihal Ozdemir, I.U. Cerrahpasa Tip Fakultesi Hastanesi, C ¸ ocuk Hematoloji BD, 34098 Fatih/Cerrahpasa, Istanbul, Turkey. E-mail: [email protected]
Downloaded by [ECU Libraries] at 20:46 11 September 2015
I. Yildiz et al.
terms of “acute” and “chronic” ITP [1]. The etiology is unknown, but the newly diagnosed ITP may follow an antigenic challenge such as infection or vaccination within a few weeks. The immune mechanisms that play role in the initiation of the disease are the targets of therapy when indicated. There are several treatment strategies used for the newly diagnosed patients as firstline therapy, including observation alone, corticosteroids, intravenous immunoglobulin (IVIG), and anti-RhD immunoglobulin (anti-D IgG). High-dose pulse methylprednisone (HDMP) therapy was first used by Ozsoylu from Turkey [3–5] and other authors [6, 7] and was quite successful in raising the platelet counts. Imbach and Blanchette [8, 9] and their colleagues proposed high-dose IVIG treatment (0.8–1 g/kg) and showed a success rate of 80%. Other modalities of treatment include anti-D IgG therapy [10–13] and cytostatics such as vinca alkaloids and chlorambucil [14]. Splenectomy is usually reserved for children with persistent or refractory ITP when first-line treatment options fail [15]. New treatment modalities such as rituximab, eltrombopag, or romiplostim are currently used mostly in adult patients and more rarely in pediatric patients [16–18]. Although there are several guidelines published for the treatment of acute ITP, there is still considerable controversy on which pediatric patients should be treated and what is the most appropriate therapeutic agent. Observation is recommended unless the child has active bleeding and/or wet purpura; however, some physicians still choose to treat a platelet count for the rare risk of life-threatening bleeding or parent anxiety. Cerrahpasa Medical Faculty is a university hospital and tertiary center to where about 15–20 new cases of ITP are referred every year. The aim of this study is to present our own center’s experience of 32 years to evaluate the treatment options for this common disease. MATERIALS AND METHODS This retrospective study aimed to analyze children (3 months to 18 years) who were diagnosed and treated for ITP at Cerrahpasa Medical Faculty, Pediatric Hematology Unit, between 1978 and 2010. These included patients seen and treated at outpatient setting as well as children hospitalized for ITP. A total of 541 medical records were available for review. Demographic data, bleeding manifestations, any history of antecedent infection or vaccination, initial and follow-up platelet counts, treatment on the first visit, platelet response to therapy, complications related to ITP, and final outcome from the time of presentation were recorded. Because the patients included in this study were classified as acute/chronic before the newer terms were proposed and were managed accordingly, older classification was used for the purpose of this retrospective study. Chronic ITP was defined as thrombocytopenia persisting for longer than 6 months following initial diagnosis. Patients were also classified as acute ITP if their platelet counts normalized due to therapy (normal platelet count in the last 4 weeks without treatment) when they don’t have a follow-up platelet count at 6 months. Bone marrow aspiration, Coombs test, antiplatelet antibodies, antinuclear antibodies, viral serology, and immunoglobulins were investigated in selected cases. Bone marrow aspirates were performed in children with atypical features to exclude other hematological diseases or before initiation of corticosteroid treatment. Therapy at initial diagnosis was administered to patients with platelet counts
